Diagnosing IBS and targeting gut microbiota and metabolites to improve symptoms

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The educational content in this post, elaborated in collaboration with Bromatech, was independently developed and approved by the GMFH publishing team and editorial board.

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Getting diagnosed with IBS

The use of symptom-based criteria for the diagnosis of gastrointestinal functional disorders may help physicians to diagnose and legitimize such disorders, and not be seen only as a combination of symptoms. A major improvement toward the understanding of these disorders was introduced by the criteria of the Rome Foundation. Many criteria have been adopted and the last ones are related to the Rome IV criteria (2016). Rome IV changed the terminology from functional disorders to disorders of gut-brain interaction (DGBI) since the term “functional” implied illegitimacy and stigmatized the patients¹.

Even though a diagnosis could be made with the mentioned criteria, certain examinations may be helpful to exclude not only inflammatory bowel diseases and celiac disease, but also bile acid diarrhea, congenital sucrose-isomaltase deficiency, histamine mediated disorders, systemic nickel allergy and high stool burden related to pelvic floor dysfunction³. It has also been described that post-infective IBS and may occur in approximately 11% of people suffering an acute infection⁴. Recent studies also showed that COVID-19 might increase the risk of developing chronic intestinal symptoms and IBS^5,6.

Many patients diagnosed with IBS may also look for further diagnosis. However, when physicians identify patients’ complaints as factual and can make a diagnosis based on these criteria, providing empathy, engaging the patient in patient-centered interaction by describing the mechanisms of the disorder and by finding possible solutions to improve the physiological condition, those patients are more likely to accept the diagnosis.

When the illness becomes easier to understand, it is also treated more appropriately! The good news is that the positive diagnosis of IBS using symptom-based criteria and limited investigation is durable and safe, highlighting that IBS is not associated with the development of organic gastrointestinal disease².

IBS subtypes and overlapping symptoms influence their management in clinical practice

IBS is classified into 4 subtypes based on predominant bowel habits:

• IBS with predominant constipation
• IBS with predominant diarrhea
• IBS with mixed bowel habits
• IBS unclassified

Moreover, there is functional diarrhea and constipation when these symptoms are not associated to pain. Functional abdominal bloating and distension are diagnosed only if these are the predominant symptoms and neither is required to make the diagnosis of IBS.

To meet the diagnostic criteria of IBS according to Rome IV, the following symptoms need to be present: abdominal pain, on average at least 1 day a week in the past 3 months (with the first onset at least 6 months before diagnosis), associated with two of the following symptoms: pain related to defecation, change in frequency of stool or change in form (appearance) of stool¹.

 

Targeting the gut microbiota to improve IBS symptoms

Although the etiology of IBS remains in part unknown, understanding the potential mechanisms has progressed rapidly over the years involving the gut microbiota, the gut-brain axis, the altered intestinal motility, the epithelial barrier, the immune system, the enteric nervous system, certain food antigens, and psychological and genetic factors⁷.

The post-infective IBS model shows the central role of an alteration of gut microbiota as a leading mechanism for IBS. Other clinical scenarios linking IBS to gut microbiota include the increased risk of IBS induced by systemic antibiotics and IBS symptom improvement after taking probiotics or non-absorbable antibiotics.

Microbiota dysbiosis in IBS has been recognized by the Rome Foundation as a plausible factor contributing to the disorder⁸. Experiments with animal models, aimed to indicate the importance and possible etiological role of the microbiota in IBS, have proven that the colonization of germ-free animals with microbiota from IBS patients can induce visceral hypersensitivity, impair intestinal permeability, and alter gastrointestinal transit time⁹.

Specific bacteria (e.g., a decrease in Bifidobacterium and Faecalibacterium genus and an increase in Lactobacillaceae family, Bacteroides genus and Enterobacteriaceae family) have been associated with the gut microbiomes of patients with IBS, although it is too early to determine if these microbes are a product or cause of IBS¹⁰. It is also interesting to note that IBS symptoms severity is related to specific traits of gut microbiota composition (i.e., low microbial richness and Bacteroides enterotype enriched) and function (i.e., low methane exhaled), which highlights the potential of modulating gut microbiota as means to improve IBS symptoms and the quality of life of these patients.

The involvement of the gut microenvironment in IBS symptoms has led to the publication of a range of studies that suggest antibiotics, prebiotics and prebiotics may exert their therapeutic activity through their impact at the level of gut microbiota composition, microbial metabolism products (e.g., short-chain fatty acids) and gut barrier integrity. However, the use of these gut microbiome-based treatments is not always universally approved. This is the case of rifaximin as non-absorbable antibiotic for IBS as its use is based on a potential capacity of changing an altered gut microbiota but more clinical studies are needed to better establish our understanding on the therapeutic role of antibiotics in IBS¹¹.

Future microbiome therapeutics in the pipeline for IBS include fecal microbiota transplants, microbial consortia, phages and engineered bacteria, while these strategies are still under study to translate their physiological effects into a possible clinical practice. For instance, Quigley and colleagues recently found the next generation probiotic Blautia hydrogenotrophica (MRx1234) is a new potential safe therapeutic option for patients with IBS-constipation, IBD-D or those who have mixed symptoms¹².

Recent studies also support other novel targets of potential interest for managing IBS symptoms. Histamine produced by specific gut bacteria has been involved in abdominal pain, which suggests the role of targeting bacterial histamine for managing abdominal pain in IBS. Also, following a low FODMAP diet was superior to the spasmolytic agent otilonium bromide in improving symptoms in patients with IBS in primary care. Sequestering harmful molecules in the gut environment through an intestinal adsorbent has also shown promising in improving stool consistency, abdominal pain, stool frequency and urgency in patients with IBD-predominant diarrhea. Overall, these findings suggest the potential of impacting gut microbiota and metabolites as means of improving IBS symptoms¹³.

Take-home messages

• The use of symptom-based criteria for IBS helps physicians to make a diagnosis with limited investigations.
• Certain examinations may be helpful as a support to exclude less common organic diseases.
• IBS can have a slow-onset or a rapid-onset which is often related to infections (post-infective IBS).
• An altered gut microbiota composition and function appears to be involved in IBS onset and development, with specific gut microbiota profiles related to the severity of IBS symptoms.
• Future microbiome therapeutics in the pipeline for IBS include fecal microbiota transplants, microbial consortia, phages and engineered bacteria, while are not ready yet to use in the clinical practice.

References:

1. Drossman DA. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features and Rome IV. Gastroenterology. 2016 Feb 19:S0016-5085(16)00223-7. doi: 10.1053/j.gastro.2016.02.032. Epub ahead of print.
2. Khasawneh M, Craig OF, Gracie DJ, et al. A diagnosis of irritable bowel syndrome using Rome IV criteria and limited investigations is durable in secondary care. Clin Gastroenterol Hepatol. 2023 Jun 9:S1542-3565(23)00444-5. doi: 10.1016/j.cgh.2023.05.022. Online ahead of print.
3. Camilleri M, Boeckxstaens G. Irritable bowel syndrome: treatment based on pathophysiology and biomarkers. Gut. 2023 Mar;72(3):590-599. doi: 10.1136/gutjnl-2022-328515.
4. Barbara G, Grover M, Bercik P, et al. Rome Foundation Working Team Report on Post-Infection Irritable Bowel Syndrome. Gastroenterology. 2019 Jan;156(1):46-58.e7. doi: 10.1053/j.gastro.2018.07.011.
5. Marasco G, Cremon C, Barbaro MR, et al.; GI-COVID19 study group. Post COVID-19 irritable bowel syndrome. Gut. 2022 Dec 9:gutjnl-2022-328483. doi: 10.1136/gutjnl-2022-328483. Epub ahead of print.
6. Noviello D, Costantino A, Muscatello A, et al. Functional gastrointestinal and somatoform symptoms five months after SARS-CoV-2 infection: A controlled cohort study. Neurogastroenterol Motil. 2022 Feb;34(2):e14187. doi: 10.1111/nmo.14187.
7. Chey WD, Kurlander J, Eswaran S. Irritable bowel syndrome: a clinical review. JAMA. 2015 Mar 3;313(9):949-58. doi: 10.1001/jama.2015.0954.
8. Simrén M, Barbara G, Flint HJ, et al.; Rome Foundation Committee. Intestinal microbiota in functional bowel disorders: a Rome foundation report. Gut. 2013 Jan;62(1):159-76. doi: 10.1136/gutjnl-2012-302167.
9. Crouzet L, Gaultier E, Del’Homme C, Cartier C, Delmas E, Dapoigny M, Fioramonti J, Bernalier-Donadille A. The hypersensitivity to colonic distension of IBS patients can be transferred to rats through their fecal microbiota. Neurogastroenterol Motil. 2013 Apr;25(4):e272-82. doi: 10.1111/nmo.12103.
10. Pittayanon R, Lau JT, Yuan Y, et al. Gut Microbiota in Patients With Irritable Bowel Syndrome-A Systematic Review. Gastroenterology. 2019 Jul;157(1):97-108. doi: 10.1053/j.gastro.2019.03.049.
11. Iribarren C, Maasfeh L, Öhman L, et al. Modulating the gut microenvironment as a treatment strategy for irritable bowel syndrome: a narrative review. Gut Microbiome. 2022; 3:e7. doi: 10.1017/gmb.2022.6.
12. Quigley EMM, Markinson L, Stevenson A, et al. Randomised clinical trial: efficacy and safety of the live biotherapeutic product MRx1234 in patients with irritable bowel syndrome. Aliment Pharmacol Ther. 2023; 57(1):81-93. doi: 10.1111/apt.17310.
13. Simrén M. Targeting the gut microenvironment in IBS to improve symptoms. Nat Rev Gastroenterol Hepatol. 2023; 20(2):69-70. doi: 10.1038/s41575-022-00718-3.